A very large, fraction of published literature on cellulose is devoted to softwood, hardwood, and cotton based cellulose, as these have higher molecular weights and are generally more suited for synthesizing various polymeric derivatives. Most cellulose production industries worldwide are still based on wood. Today, however, lignocellulose like sugarcane bagasse and other agricultural residues/non-woods derived celluloses are considered key raw materials for producing cellulose pulp, as they are annually renewable and considered more environment-friendly in comparison to wood.
Lignocellulose is composed mainly of cellulose, hemicellulose and lignin. The lignocellulose biomass or substrate is selected from agricultural residues such as corn stover and sugarcane bagasse, energy crops, wood residues such as saw mill and paper mill discards, and municipal paper waste.
Ververis C, et al. (2004) in industrial crops and products 19:245-254 discloses fiber dimensions, lignin and cellulose content of various plant materials and their suitability for paper production.
The high molecular weight wood material takes much more time to get replenished by nature, and separate land has to be set aside for their cultivation. On the other hand agricultural residues such as sugarcane bagasse and corn cobs do not need separate land as they are by-products of agricultural crops. While sugarcane bagasse and other non-wood biomass are known to possess lower molecular weights than wood celluloses, cellulose derived from these sources can substitute wood cellulose in several applications, particularly as carboxy celluloses in wound dressing gauzes, oxidized nanocelluloses for use in biocomposites, antimicrobial coatings, certain low molecular weight grades of high-volume soluble cellulose derivatives such as cellulose ethers like carboxymethyl cellulose, and also lead to newer applications, to replace petroleum derived products.
Low molecular weight oxidized celluloses have the advantage that they are more likely to swell or dissolve in organic solvents or dilute alkali solutions, thereby enabling their further facile transformations into several other new functional derivatives with new properties for further exploitation. Availability of industrial quantities of these celluloses will spur ever greater interest in re-visiting these materials as major industrial chemicals.
There exists a plethora of patents and papers published over the past decades on synthesis, manufacturing processes and applications of oxidized celluloses.
Accordingly the oxidation of cotton linters, hardwood cellulose, and softwood cellulose is reported in some of the prior art. Synthesis of sodium nitrite based oxidation of cellulose have been reported since the 1940's, such as using gaseous nitrogen dioxide at 20° C., wherein a maximum carboxy content of 21.8% was obtained; using nitric acid with sodium nitrite system at 20° C., wherein a carboxy content of 18.32% which has been reported by Pigman W W in J Am Chem Soc 71:2200 (1949).
Another variation based on ortho-phosphoric acid (85%) and sodium nitrite was investigated in the art where specificic C6 oxidation was difficult. A. C. Besemer et al. in Cellulose Derivatives Chapter 5, pp 73-82 Apr. 17, 1998 describes selective oxidation of the substrate at the 6-position of the glucose unit in presence of concentrated phosphoric acid with nitrite/nitrate. However, the reaction is not completely specific, since some oxidation at the secondary hydroxylic groups occurs. Further borohydride reduction of the product restores the diol configuration also β-elimination is avoided and thereby depolymerization. Oxidation with sodium hypochlorite and bromide as a catalyst and TEMPO as a mediator is also applicable to cellulose.
Further, oxidation of softwood pulp or cotton linters derived cellulose was carried by using HNO3/H3PO4/NaNO2 led to a maximum of 21.6% carboxyl content, while the HNO3/H2SO4/NaNO2 gave a maximum of 21.1% carboxy content.
U.S. Pat. No. 6,379,494 (Jewell, Richard A. et al.) reported use of TEMPO (2,2,6,6-tetramethylpiperidinyloxy free radical) as a primary oxidant and a hypohalite salt as a secondary oxidant for making carboxylated cellulose fibers from bleached northern softwood kraft pulp. Influence of oxidation time on selective oxidation of regenerated cellulose with NO2/CCl4 as oxidation system is disclosed in Fibers and Polymers May 2012, 13, (5), pp 576-581 by Ya Dong Wu. Oxidation of cellulose by acid-sodium nitrite systems is also reported by J. H. Arendt et al. Journal of Polymer Science: Polymer Symposia 42, 3, 1521-1529, 1973
On the other hand, Y W Sitotaw (2011) discloses the synthesis of carboxymethyl cellulose (CMC) from sugarcane bagasse, using sodium monochloroacetate and sodium hydroxide and a process for fractionating sugarcane bagasse into high α cellulose, xylan and lignin is reported in 1893/DEL/2007.
The conversion of tricarboxy cellulose from dicarboxy or dialdehyde cellulose compound is known in the literature. WO/2012/119229 discloses the method for preparation of 2,3,6-tricarboxycellulose (TCC) by 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical-mediated oxidation of periodate-oxidized chlorite-oxidized pulp (i.e. 2,3-dicarboxycellulose) at 60° C. for alternatively 5, 10, 5, 20 and 45 hours to liberate nanofibrillar cellulose (NFC). The preparation of haemostatic agent such as 2,3,6-tricarboxy cellulose by NO2 oxidation of 2,3-dialdehyde cellulose is reported by Sinha T J in Biomater Med Devices Artif Organs. 1984-1985; 12 (3-4):273-87.
Further, oxidation of dialdehyde cellulose gives di- or tricarboxy cellulose is disclosed by Tajima, K. in Journal Name: J. Appl. Polym. Sci.: Appl. Polym. Symp Journal vol 37; Conference: 9, May 1982. Russian Patent No. RU2146264 discloses the preparation of highly oxidized cellulose in presence of sodium periodate solution and solution of nitrogen oxides in carbon tetrachloride. The TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl radical)-mediated oxidation of wood celluloses to nanofibers 3-4 nm published by Isogai et al. 2011 Nanoscale, 2011, 3, 71-85).
Article in Green Chem., 2012, 14, 300-303 by Robert J. Crawford discloses formation of shear thinning gels from partially C-6 oxidized cellulose nanofibrils. Jianguo Zhang et al in Carbohydrate Polymers 69 (2007) 607-611 reported procedure for synthesizing (cotton) hydrolyzed cellulose nanospheres with size ranging from 60 nm to over 570 nm.
Further nanofibers of oxidized celluloses are a subject of intense recent interest due to their potential for applications in severe areas high performance materials, such as gas barrier films, for example coatings for polyesters like poly (lactic acid) with very low oxygen permeability, hemostatically efficient materials with no pathological response, as a material to fractionate and purify proteins, enzymes, hemoglobins, hormones etc.
The larger nanoparticle sizes that have been obtained so far were likely to be due to the higher molecular weights of the starting cellulose, as they were based on tunicate and bacterial cellulose.
Vijay Kumar et al, (2002) in Carbohydrate Polym 48:403-412 discloses reaction of cellulose (cotton linter sheet) with a mixture of HNO3/H3PO4—NaNO2 (2:1:1.4, v/v/% w) at room temperature for different time intervals in to get oxidized cellulose with particle size ranging from 74 and 105 μm. However the inventors used lower molecular weights of non-wood celluloses as well as cotton cellulose and their oxidized derivatives which lead to smaller nanoparticles.
U.S. Pat. No. 7,662,801 (Kumar et al) reported use of a series of oxidized cellulose esters as a drug carrier in the development of biodegradable controlled and/or sustained release pharmaceutical, agricultural, and veterinary compositions, whereas Anderson et al (1946) Science 104 (2700), 301 reported substantial use of oxidized cellulose in surgery of the uterus in both cases the source of the cellulose is either softwood or hardwood pulp or cotton.
Functionalized nanocellulose technology appears to be destined to remain a key area of cellulose research due to innumerable possible applications.
In literature several interesting features were noted with progressive changes in oxidation levels as well as by introducing multifunctionalities. The functionalization of cellulose via use of several types of oxidation reagents can indeed lead to a wide variety of polymeric structures, with the following parameters: (i) type of functional groups incorporated, (ii) extent of functional groups incorporated, (iii) distribution of functional groups along the cellulosic polymer chain, (iv) the molecular weight distribution of the resulting oxidized cellulose, (v) particle size distribution (and whether nanofibers or nanoparticles are formed), (vi) morphology of the resulting oxidized cellulose, and (vii) solubility in aqueous/non-aqueous media. Such explosive variety of new structural features can in turn provide an array of properties to cellulose, which can be a sustainable source of multifunctional polymers and nanosized materials.
It was observed that aldehyde, carboxy, and amine functionalized wood cellulose as reinforcements in epoxy composites shown interesting advantages as compared to the use of unfunctionalized (See “Curing characteristics of epoxy resins filled with cellulose and oxidized cellulose, A. J. Varma et al., Angew. Makromol. Chem., (1984), 122, 211-218)
As observed for other cellulose nanoparticle derivatives, spherical shapes are more likely to show stability in solvent dispersions as compared to nanofibers. Similarly, the geometrical shape of the nanoparticle can play a role in drug delivery and biomedical applications.
The carboxycellulose nanoparticles (6CC-NP and TCC-NP) are found efficient in stabilizing the dispersion of carbon nanotubes (SWCNT: single-walled carbon nanotubes and MWCNT: multi-walled carbon nanotubes) in aqueous media.
To overcome the technical constraints such as slow rate of oxidation or degradation, expensive reagent, poor solubility, slow reaction rate, poor yield, large particle size due to high molecular wt. cellulose, less carboxy content the present inventors have developed a process for synthesis of nano structured oxidized cellulose from lower molecular weight and lower crystalline cellulose derived from sugarcane bagasse (94% α-cellulose) as well as cotton linters of relatively high molecular weights and successfully prepared a long series of mono- and multi-oxidized celluloses and their nanoparticles having a variety of functional groups (dialdehyde, monocarboxy, dicarboxy, tricarboxy, and carboxy-dialdehyde) in different combinations and contents, as well as their solubility behavior in organic solvents and dilute aqueous alkaline solutions. Further the inventors have employed cheap and efficient oxidizing agent to reduce the degradation with achieving substantial carboxy content of the product and yield, and obtain the product in a form that produces spherical shaped nanoparticles in a narrow size distribution of 25-35 nm and low molecular weight of 50-70 DP (degree of polymerization). Thus the instant invention is economically significant, industrially feasible and environmentally non-hazardous, and produces the product in a new form which has never been reported before for carboxycellulose, i.e. spherical shaped nanoparticles in a narrow size distribution of 25-35 nm and, low molecular weight of 50-70 DP (degree of polymerization).
Therefore, the objective of the instant invention is to provide a new process to obtain spherical/circular nano-sized oxidized cellulose from non-wood cellulose under suitable condition for wide applications.
Further carboxy cellulose product has wide applications as anti-microbial material for use in wound dressing gauze, hemostatic material, biocompatible material, biocomposites, detergent builder, catalyst, ion-exchange resin, polymer platform for making other functionalized nanoparticles of cellulose such as hydrophobic cellulose nanoparticles, etc.
U.S. Pat. No. 7,662,801 (Kumar et al) reported use of a series of oxidized cellulose esters as a drug carrier in the development of biodegradable controlled and/or sustained release pharmaceutical, agricultural, and veterinary compositions, whereas Anderson et al. in Science 104 (2700), 301 (1946) reported substantial use of oxidized cellulose in surgery of uterus, in both cases the source of the cellulose is either softwood or hardwood pulp or cotton. Additionally mechanism of the antibacterial action of mono carboxycellulose and other ion-exchange derivatives of cellulose” reported in Antibiot Med Biotekhnol. 1986 August; 31(8):624-8 by Abaev IuK. Further In vitro antimicrobial activity of oxidized regenerated cellulose against antibiotic-resistant microorganisms is disclosed in Surg Infect (Larchmt). 2003 Fall; 4(3):255-62 by Spangler D et al.
Moreover, Jarmila Vytrasova et al. (J. Ind Microbiol Biotechnol (2008) 35; 1247-1252) discloses antimicrobial properties of oxidized cellulose (6-carboxy cellulose) and its salt in linter (-L) and microsphere (-M) from OKCEL (textile form of oxidized cellulose) and tested against a spectrum of microbial strains: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Bacillus licheniformis, Aspergillus niger, Penicillium chrysogenum, Rhizopus oryzae, Scopulariopsis brevicaulis, Candida albicans and Candida tropicalis exhibited antimicrobial activity in the range of 0.1-3.5% w/v.
However, Cellulosic compounds have never been reported to be effective against bacterial species such as Mycobacterium tuberculosis (TB). These have potential to be used as inexpensive and safe drugs, as cellulose and its derivatives have been used in food products.
Further the linear 6-carboxy celluloses are known to be easy to make since celluloses are themselves linear and their use in wound dressings are well known. The anti-microbial activity of spherical/circular nanoparticles of carboxy cellulose against Bacillus, Staphylococcus aureus, Mycobacterium has been demonstrated
Therefore, the present inventors have analysed the antimicrobial activity of the carboxycellulose, and accordingly developed pharmaceutical composition comprising of nano sized spherical/circular shaped carboxycellulose derivatives that significantly inhibits the growth of microbes.